The Brain in Transition

By Kristin Sainani, PhD

Patients with schizophrenia and other psychotic disorders are known to have adverse brain changes, such as reduced volume—but it’s unclear what comes first, the disease or the abnormality. Now, for the first time, researchers have shown that the brain is actually shrinking as psychosis unfolds. The results appear in the January 10 issue of Schizophrenia Research.

“We found that people who go on to develop psychosis have a different profile of neuroanatomical changes than those who do not,” says Tyrone D. Cannon, PhD, professor of psychology, psychiatry, and biobehavioral sciences at the University of California, Los Angeles. The findings may have implications for predicting and preventing psychosis.

Cannon and his colleagues took premorbid brain MRI images of 35 individuals who had never had a psychotic episode but were considered at “ultra-high” risk based on early symptoms or a strong family history. They re-scanned their brains after an average follow-up of 1.3 years—during which time 12 developed psychosis.

Previous studies had considered losses in brain tissue density, a voxel-level measure of brain volume (typical resolution on the order of 1 cubic millimeter). Cannon’s team used a higher-resolution measure of volumetric brain change—the brain contraction rate. This parameter is calculated by transforming MRI scans into 65,000-point maps of the brain’s surface and determining how fast the surface points are contracting between sequential scans. They found that the prefrontal lobes of subjects who progressed to psychosis were contracting significantly faster—by about 0.2 millimeters per year—than those of subjects who did not progress. “Our approach allowed us to detect more subtle anatomical changes in the brain, which is critical because we would not expect the changes associated with onset of psychosis to be so gross as to be detectable using standard voxel-based methods,” Cannon says.

Though the study is interesting, it is small and lacks a healthy control group—which makes it difficult to tell how much of the detected changes are due to random variation and normal aging versus disease, comments R. Grant Steen, PhD, associate professor of psychiatry at the University of North Carolina School of Medicine. Also, it took an average of eight months to re-scan subjects with disease after their initial psychotic episode, so the timing of the changes is not entirely clear and could be related to treatment, he says.

Medication is an unlikely explanation since its use was limited and unrelated to brain contraction rates, Cannon replies. Still, he agrees, “the full significance of the findings awaits confirmation in large, multisite, longitudinal imaging studies that are currently underway.”

If the changes observed do turn out to be a cause of the onset of schizophrenia and associated disorders, “it may eventually be possible to provide treatment in high risk individuals—to delay or prevent the onset of psychosis,” Cannon concludes.